The use of microfluidic technology has been proposed for use in a number of analytical chemical and biochemical operations. These technologies provide advantages of being able to perform chemical and biochemical reactions, macromolecular separations, and the like, that range from the simple to the relatively complex, in easily automatable, high-throughput, low-volume systems. In particular, these systems employ networks of integrated microscale channels in which materials are transported, mixed, separated and detected. The small size of these systems allows for the performance reactions at substantially greater rates, and with substantially less reagent volume. Further, the development of sophisticated material transport systems has permitted the development of systems that are readily automatable and highly reproducible.
Because of their small size, microfluidic systems have typically required the use of relatively sophisticated detection systems to monitor the progress and results of the operation being performed by the system. In particular, as noted above, the extreme small scale of some microfluidic systems results in very small volumes of reagents, samples and the like, being used. Consequently, the amount of material that can be ultimately detected, e.g., using an optical detection system, is also very small. In order to address these issues, detection systems have become more sophisticated to either boost the detectable signal produced from material sought to be detected, increase the sensitivity of the instrumentation, or a combination of the two. For example, microscopes equipped with photomultipliers enhance the ability to detect fluorescently labeled materials within microscale channels. Further, the use of laser-induced fluorescence also enhances the amount of signal produced from these fluorescent materials.
Although these sophisticated detection systems have addressed many of the problems associated with detection in microscale fluidic channels, a number of problems remain, such as difficulty in optimally aligning these instruments, the cost and sophistication of providing robust optics for such systems and the like. Further, as the number of applications for microfluidic systems increases, it will include a similar increase in the type of optical detection systems to be used. The use of specifically tailored detection systems for each different application will present a likely prohibitive cost barrier. The present invention addresses many of the problems outlined above, as well as others.
The present invention provides microfluidic devices for use in performing analytical operations that employ optical detection systems. In particular, the present invention provides microfluidic devices, and systems incorporating such devices, which have at least one component of the optical detection system as a part of the microfluidic device.
In a first aspect, the present invention provides a microfluidic device which comprises a body structure having a microscale channel disposed therein. The device includes a light altering optical element integrated into the body structure adjacent to the microscale channel, whereby at least a portion of light passing from or to the microscale channel is transmitted through the light altering optical element. In preferred aspects, the body structure of the device comprises a first planar substrate having at least first and second opposing planar surfaces, the microscale channel being fabricated into the first planar surface of the first substrate, and the light altering optical element being fabricated into the second planar surface of the first substrate adjacent to the microscale channel in the first planar surface. Also included is a second planar substrate overlaying the first surface of the first planar substrate.
In an alternate aspect, a third substrate layer is provided having at least a first planar surface and a second surface. The first planar surface of the third substrate layer is bonded to one of the second planar surface of the first planar substrate or the second planar surface of the second planar substrate. The third substrate also includes a light altering optical element fabricated into the second surface of the third substrate.
In still another related aspect, the present invention also provides a microfluidic device, which comprises a body structure having an interior portion and an exterior portion. At least a first microscale channel is disposed within the interior portion of the body structure. A detection window is provided disposed on the exterior portion of the body structure, whereby the detection window provides optical access to the at least one microscale channel. In this aspect, the detection window comprises a light altering optical element integrated into the body structure.
Also provided by the present invention are microfluidic systems, which comprise a microfluidic device comprising a body structure, at least a first microscale channel disposed in the body structure, a transparent region in the body structure, the transparent region including a light altering optical element integrated into the body structure. The systems of the invention alo typically comprise an optical detector disposed adjacent to the detection window. The optical detector comprises an objective lens for collecting an optical signal transmitted from the microscale channel via the light altering optical element, and a light detector for measuring an amount of light collected.